Your Digest for Monday, Apr 22, 2024 06:59 PM


⭐Manifestations of diabetic neuropathy

  1. Earliest is ⭐loss of vibration sense and pain (deep before superficial) and temperature
  2. ⭐Later - loss of proprioception.
    2. ⭐Small muscle wasting is also seen in the hands
  3. Can present with ⭐IMPROVEMENT of glycaemic control but remits with continue glycaemic control

Phase I - double digits (<100)
Phase II - Triple digits (<300)
Phase III - quadruple digits, also C being the 3rd letter of the alphabet, phase III trials 'compare' efficacy -> RCTs. (<3000)
3. Phamacokinetic testing to determine ADME characteristics (absorption, distribution, metabolism and elimination)
Phase 3 = 1000-3000 to confirm effectiveness, monitor side effects and compare with other treatments. (⭐therapeutic confirmation - Randomized controlled trials; efficacy, safety)

[!INFO] Mmemonic: Bag of flowers
MuscleSpindle.gif




- **Tau protein** is a protein which stabilizes microtubules and regulates protein binding to microtubules in healthy cells. 

[!INFO] Tau causes Tangles; APP causes Plaques



Other causes of subtotal villous atrophy

CausesOfSubtotalVillousAtrophy.png


  1. AL amyloidosis <- The most common form.
    Other types of amyloidosis:

[!INFO] AL Vs AA : importance of differentiating
AL amyloidosis must be differentiated from other forms of amyloidosis (eg, AA amyloidosis, ATTRmt amyloidosis, and ATTRwt amyloidosis) since the latter are non-neoplastic and will not benefit from chemotherapy.

amyloidosisEvaluationAlgorithm.png

[!INFO] Once the presense of amyloid is found
amyloidPrecursorProtein.png
the precursor protein must be determined.
(Both (AL and AA) have the beta pleted sheet structure) (Harrison's - page 804)

[!INFO] AL Amyloidosis and mutliple myeloma are closely related but NOT the same.


Muscle excitation contraction and neuromuscular junction

SarcoplasmTTubulesTriadSarcolemmaMuscleNeuromuscularJunction.png

Source

[!INFO] What is calcium induced calcium release?
CICR is considered to be the physiological mechanism of Ca2+ release in cardiac muscle. It is generally agreed that an influx of Ca2+ through L-type voltage-dependent Ca2+ channels on the surface and the t-tubule membrane of myocytes activated by an action potential triggers Ca2+ release from the SR by the CICR mechanism to cause cardiac contraction (13, 20, 62, 226, 252). In skeletal muscle where CICR was first discovered, however, the primary mechanism of physiological Ca2+ release is not CICR, but direct protein-protein interaction between the voltage sensor of the t-tubule membrane, the dihydropyridine receptor (DHPR), and the Ca2+ release channel of the SR membrane, the ryanodine receptor (RyR). Source

Even in normal physiology, during repetitive nerve impulses there is a progressive depletion of stored acetylcholine (ACh), causing a decreased number of quanta released from each impulse resulting in a reduction in amplitude of the endplate potentials. (but it remains above the threshold required to elicit a muscle action potential)Source


EffectOfLiverBloodFlowOnExtractionRatioDerangedPhysiology.png

Source
Pharmacological efficacy (also called Intrinsic efficacy) is


ventilationPerfusionVQRatioCombinedGraph.jpg
[[2018-OCT-BSQ#Pulmonary vascular resistance]]


Pathophysiology of NAFLD

Insulin resistance is the key prerequisite for NAFLD.

  1. Dyslipidaemia (Low HDL and high TGL)